Role for autocrine TGF‐β1 in regulating differentiation of a human leukemic cell line toward osteoclast‐like cells

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Abstract
Increasing evidence suggests that transforming growth factor‐β (TGF‐β) is involved in bone formation during remodeling. Using a recently cloned human leukemic cell line (FLG 29.1 cells) we demonstrate that these cells synthesize and secrete TGF‐β1 and that exogenous or autocrine TGF‐β1 can induce the same features of osteoclastic‐like cells, exerting its effects through the binding to TGF‐β specific receptors. Scatchard analysis of 125I‐labeled TGF‐β1 to FLG 29.1 cells revealed the presence of a single high affinity binding site with a Kd value of ∼25 pM and a binding capacity of ∼900 sites/cell. Affinity labeling experiments showed that FLG 29.1 cells express type I and type II TGF‐β receptors. Stimulation of FLG 29.1 cells with low TGF‐β1 doses reduced cell proliferation and increased cell adhesion and tartrate resistant acid phosphatase (TRAcP) activity. Pretreatment of FLG 29.1 cells with TGF‐β1 caused a significant and dose‐dependent response to calcitonin. Northern blot of total mRNA and analysis of the conditioned media (CM) showed that TGF‐β1 was synthesized by FLG 29.1 cells. TPA treatment, which induces partial differentiation of these cells, markedly increased TGF‐β1 mRNA expression and growth factor release. The majority of TGF‐β1 secreted by TPA‐treated cells was in its latent form. However, anti‐TGF‐β antibodies inhibited TGF‐β1 and TPA‐induced growth inhibition, calcitonin responsiveness, and TRAcP activity, suggesting that the TPA effect is mediated in part by autocrine TGF‐β1 and indicating that the cells can activate and respond to the TGF‐β that they secrete. These findings support a potential autocrine role for TGF‐β1 in osteoclast differentiation.
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